MICROBIAL PATHOGENESIS
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2022
·
IF 3.848
Ting Qin,Kai Chen,Bingwen Xi,Liangkun Pan,Jun Xie
The inter-kingdom communication between host and pathogenic bacteria mediated by the host hormones epinephrine (Epi)/norepinephrine (NE)/autoinducer-3 (AI-3) and transduced by the bacterial two-component signal transduction system QseBC has been well demonstrated in mammalian pathogens . Aeromonas hydrophila , a common opportunistic pathogen in freshwater aquaculture, responds to NE by increased bacterial growth and enhanced virulence. However, the underlying mechanisms remain poorly understood. Our study demonstrated that deletion of qseB and qseC significantly inhibited NE-promoted growth, biofilm formation, and hemolytic activity of A. hydrophila . The adhesion ability of Δ qseB and Δ qseC to J774a.1 cells was significantly decreased compared with the wild-type strain in the presence and absence of NE, whereas NE still enhanced the adhesion ability of the mutant and wild-type strains with a similar effect, suggesting that NE-enhanced cell adhesion was independent of QseBC. Moreover, QseBC did not affect the swimming and swarming motility of A. hydrophila with or without NE. Quantitative real-time PCR analyses revealed the down-regulated expression of some virulence-related genes ( hly , ast , act , aerA ) in each mutant compared with the wild-type strain in the presence of NE. Tilapia infection experiments indicated that deletion of qseB or qseC weakened NE-promoted virulence of A. hydrophila . In conclusion, our study suggests that NE stimulates the growth, biofilm formation, and hemolytic activity of A. hydrophila and enhances the virulence of the pathogen in fish via the QseBC system.
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AQUACULTURE INTERNATIONAL
·
2024
·
IF 2.2
Cui Jun,Zeng Dan,Guan Peipei,Jiang Ning
Exposure to pathogens induces hyperactivate inflammatory immune responses, oxidative stress and even death in fish. Therefore, suppressing excessive inflammatory responses is a means of treating fish diseases. Scutellariae Radix (SR), an herbal medicine, has anti-inflammatory and antioxidant properties. However, the active ingredients of SR that produce a marked effect and their mechanisms are poorly understood. In this study, 32 active ingredients of SR and their 124 target genes associated with anti-inflammatory effect were screened. These target genes in zebrafish were mainly enriched in biological processes associated with response to stress and stimulus. The KEGG enrichment analysis and pathway–pathway network analysis showed that the MAPK signalling pathway and nine other pathways were the key pathways associated with anti-inflammatory effect. A protein–protein interactions (PPI) network of target genes was constructed, and AKT2 and nine other genes were identified as the hub genes by cytoHubba. Combining the above results, we constructed an active ingredient–hub protein–key pathway network, showing that wogonin-AKT2 was the key regulated module. Molecular docking and SPR-based assays were used to investigate the possible interaction of wogonin with the AKT2 protein. The infected zebrafish and grass carp treated with wogonin displayed a higher survival rate and anti-inflammatory and antioxidant effects than the infected fish without wogonin treatment. Dietary wogonin also enhanced grass carp anti-inflammatory and antioxidant effects. These findings further reveal the molecular biological mechanism by which wogonin from SR exerts anti-inflammatory effects and provide a theoretical basis for the prevention of fish diseases.
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Frontiers in Microbiology
·
2025
·
IF 4.5
Guang Yang,Ying Huang,Ning Ma,Kai Li,Xiao-mei Wang,Lian-bo Zhang,Wen-bo Yang,Wan-li Zhang,Lei Xia,Hong-Yu Zhang,Li-lai Yuan
Aeromonas hydrophila is a major pathogen responsible for significant economic losses in global aquaculture. Inhibitory and bactericidal activities of seven disinfectants were tested against 10 aquatic pathogens, including A. hydrophila, A. veronii, A. salmonicida, A. sobria, Edwardsiella tarda, E. ictaluri, Pseudomonas aeruginosa, and Yersinia ruckeri. Minimal effective concentrations were determined via quantitative suspension tests, while a scale-trauma zebrafish model assessed in vivo protection. Methylene bis(thiocyanate) (MBT) exhibited the strongest antimicrobial activity, with minimum inhibitory concentrations and minimum bactericidal concentrations of 0.1–0.4 mg/L and 0.2–0.8 mg/L, respectively. At 0.01 mg/L, MBT achieved a 3-log pathogen inactivation, equivalent to 0.2 mg/L Trichloroisocyanuric acid (TCCA). In vivo, 0.01 mg/L MBT provided 100% protection in zebrafish after 6 and 12 h exposure, whereas 0.2 mg/L TCCA yielded 95.83 ± 3.61% survival after 1 h. The safe concentrations of MBT and TCCA for zebrafish were 0.0364 and 0.0677 mg/L, respectively. The results showed that both TCCA and MBT effectively controlled A. hydrophila infection; however, MBT demonstrated greater potential for aquaculture applications due to its lower effective concentration (0.01 mg/L) and reduced sensitivity to interference from organic matter. In addition, this study presents a systematic protocol for evaluating the efficacy of disinfectants.
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MOLECULAR & CELLULAR PROTEOMICS
·
2022
·Vol. 21
·期 9
·
IF 7.381
Lishan Zhang,Zujie Yao,Huamei Tang,Qingli Song,Huanhuan Song,Jindong Yao,Zhen Li,Xiaofang Xie,Yuexu Lin,Xiangmin Lin
Protein lysine acetylation (Kac) modification plays important roles in diverse physiological functions. However, there is little evidence on the role of Kac modification in bacterial antibiotic resistance. Here, we compared the differential expressions of whole-cell proteins and Kac peptides in oxytetracycline sensitive and oxytetracycline resistance (OXYR) strains of Aeromonas hydrophila using quantitative proteomics technologies. We observed a porin family protein Aha1 downregulated in the OXYR strain, which may have an important role in the OXY resistance. Interestingly, seven of eight Kac peptides of Aha1 decreased abundance in OXYR as well. Microbiologic assays showed that the K57R, K187R, and K197R Aha1 mutants significantly increased antibiotic resistance to OXY and reduced the intracellular OXY accumulation in OXY stress. Moreover, these Aha1 mutants displayed multidrug resistance features to tetracyclines and β-lactam antibiotics. The 3D model prediction showed that the Kac states of K57, K187, and K197 sites located at the extracellular pore vestibule of Aha1 may be involved in the uptake of specific types of antibiotics. Overall, our results indicate a novel antibiotic resistance mechanism mediated by Kac modification, which may provide a clue for the development of antibiotic therapy strategies.
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Frontiers in Immunology
·
2023
·
IF 7.3
Zhang Lishan,Sun Lina,Srinivasan Ramanathan,Lin Meizhen,Gong Lanqing,Lin Xiangmin
Bacterial AraC is a transcription factor family that initiates transcription by recruiting RNA polymerase to the promoter and directly regulating various bacterial phenotypes. It also directly regulates various bacterial phenotypes. However, how this transcription factor regulates bacterial virulence and affects host immunity is still largely unknown. In this study, deleting the orf02889 (AraC-like transcription factor) gene in virulent Aeromonas hydrophila LP-2 affected several important phenotypes, such as increasing biofilm formation and siderophore production abilities. Moreover, Δorf02889 also significantly decreased the virulence of A. hydrophila and has promising attenuated vaccine potential. To better understand the effects of orf02889 on biological functions, a data independent acquisition (DIA)-based quantitative proteomics method was performed to compare the differentially expressed proteins between Δorf02889 and the wild-type strain in extracellular fractions. The following bioinformatics analysis suggested that ORF02889 may regulate various metabolic pathways, such as quorum sensing and ATP binding cassette (ABC) transporter metabolism. Moreover, 10 selected genes from the top 10 decreasing abundances in proteomics data were deleted, and their virulence to zebrafish was evaluated, respectively. The results showed that ΔcorC, Δorf00906, and Δorf04042 significantly reduced bacterial virulence. Finally, the following chromatin immunoprecipitation and polymerase chain reaction (ChIP-PCR) assay validated that the promoter of corC was directly regulated by ORF02889. Overall, these results provide insight into the biological function of ORF02889 and demonstrate its inherent regulatory mechanism for the virulence of A. hydrophila.
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FISH & SHELLFISH IMMUNOLOGY
·
2022
·
IF 4.622
Yipeng Gu,Kai Chen,Bingwen Xi,Jun Xie,Xuwen Bing
Paeonol, a naturally occurring polyphenol isolated from medical plant , has been known to exhibit anti-oxidative and anti-inflammatory effects. In order to evaluate the effect of paeonol on Carassius auratus gibelio infected by pathogenic bacteria Aeromonas hydriphila . 750 fish were randomly divided into 5 groups, which separately treated with 0.85% sterile saline (blank), A. hydriphila (negative control), A. hydriphila with paeonol (4 mg/kg, 64 mg/kg), and A. hydriphila with enrofloxacin (12 mg/kg, positive control). Fish were anaesthetized with MS-222 (100 mg/L), and samples were collected at 6 and 72 h after A. hydriphila challenge. The results showed that compared with the negative group, the survival in paeonol groups marked increased by 14.75% and 18.94%. The plasma immunoglobulin M (IgM) was notably increased, and low density lipoprotein (LDL) was significantly decreased in paeonol groups at 6 h ( P < 0.05). The antioxidative enzymes catalase (CAT), total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-Px) were significantly increased in paeonol groups at 6 h, while malondialdehyde (MDA) and myeloperoxidase (MPO) contents were lower ( P < 0.05). The inflammatory related genes MyD88 and TLR-5 were significantly downregulated, and the TLR-3 was significantly increased in paeonol groups at 72 h ( P < 0.05). In addition, histopathological analyses showed that the lesion in liver, spleen and caudal kidney were considerably attenuated in paeonol groups. In conclusion, paeonol could increase the survival rate, mitigate oxidative damage, inflammation, tissue lesions, and improve the immunity of gibel carp challenged with A. hydrophila .
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FOLIA MICROBIOLOGICA
·
2015
·Vol. 61
·期 3
·249-253
·
IF 1
Hu Ruixue,Du Na,Chen Nan,Lin Li,Zhai Yanhua,Gu Zemao
The mechanisms of resistance to levofloxacin for Aeromonas hydrophila isolated from diseased fish and selected in vitro were examined in this study. Levofloxacin-resistant mutants were obtained by selection of A. hydrophila in vitro. The quinolone resistance-determining regions (QRDRs) of the gyrA and parC genes were sequenced in Lev R strains and reverse mutation strains. All Lev R strains carried a point mutation at codon 83 (Ser → Ile), and one strain (25 %) harbored a mutation at position 92 (Leu → Met) in the GyrA-QRDR. After being transferred in a levofloxacin-free medium, one strain of the mutants was successfully reversed and the reversion was related with mutations o f GyrA-QRDR at positions 81 (Gly → Asp) and 83 (Ile → Ser). No amino acid alteration was found in the ParC-QRDR. In addition, the minimum inhibitory concentration (MIC) of levofloxacin for the mutants was lower in the presence of reserpine, and all mutants were also resistant to some of the other quinolones. It was found that the mechanism of levofloxacin resistance of A. hydrophila selected in vitro was related to gyrA of type II topoisomerase, and an efflux mechanism was involved in the resistance as well.
研究领域:
微生物学
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分子生物学
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药理学
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水产病害防治
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抗菌药物耐药性
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Frontiers in Cellular and Infection Microbiology
·
2016
·
IF 5.218
Dong Yuhao,Liu Jin,Pang Maoda,Du Hechao,Wang Nannan,Awan Furqan,Lu Chengping,Liu Yongjie
The growth-stimulating effects of catecholamine stress hormones have been demonstrated in many pathogens. However, catecholamine-induced growth and its underlying mechanisms remain poorly understood in Aeromonas hydrophila. The present study sought to demonstrate that norepinephrine (NE), epinephrine (Epi), dopamine (Dopa), and L-dopa stimulate the growth of A. hydrophila in iron-restricted media containing serum. NE exhibited the strongest growth stimulation, which could be blocked by adrenergic antagonists. Furthermore, it was demonstrated that NE could sequester iron from transferrin, thereby providing a more accessible iron source for utilization by A. hydrophila. The deletion of the amoA gene associated with amonabactin synthesis revealed that the amonabactin siderophore is not required for NE-stimulated growth. However, the deletion of the TonB2 energy transduction system resulted in the loss of growth promotion by NE, indicating that a specific TonB-dependent outer membrane receptor might be involved in the transport of iron from transferrin. Collectively, our data show that catecholamine sensing promotes the growth of A. hydrophila in a manner that is dependent on the TonB2 energy transduction system.
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JOURNAL OF FISH DISEASES
·
2025
·
IF 2.2
Bo Li,Penghui Yu,Lei Su,Jianguo Su,Yu Gao,Gailing Yuan
Aeromonas hydrophila- induced bacterial sepsis is a major threat to aquaculture, characterised by excessive inflammation, ferroptosis (an iron-dependent lipid peroxidation-driven cell death) and oxidative damage, which collectively lead to high mortality. Taurine (TAU) and glutathione (GSH) have been demonstrated to have potential therapeutic efficacy against ferroptosis-associated pathologies through redox modulation. However, their combined effects and underlying mechanisms in alleviating A. hydrophila infection remain unclear. In this study, we investigated the protective roles of TAU, GSH and their combination in vitro using yellow catfish ( Pelteobagrus fulvidraco ) macrophages and grass carp ( Ctenopharyngodon idella ) kidney (CIK) cells and in vivo using yellow catfish challenged with A. hydrophila . The results showed that TAU and GSH, either alone or in combination, alleviated oxidative stress by significantly reducing reactive oxygen species (ROS) accumulation and inhibited nuclear factor-κB (NF-κB) pathway activation. This led to downregulated expression of pro-inflammatory cytokines ( IL- 1β and TNF -α) and upregulated anti-inflammatory cytokines ( IL- 10 and TGF -β), accompanied by alleviated ferroptosis. In vivo, dietary supplementation with TAU (10 g/kg) or GSH (350 mg/kg) alone improved survival rates (51.7% and 38.3%, respectively), reduced tissue bacterial loads and protected intestinal and hepatic tissues by preserving mucosal barrier function. However, the TAU + GSH combination unexpectedly decreased survival (28.3%) due to excessive immunosuppression (overproduction of IL- 10 and TGF -β) and impaired mucosal barrier, which exacerbated pathogen colonisation. Together, our findings demonstrate that TAU and GSH alleviate A. hydrophila -induced oxidative stress by reducing mitochondrial ROS overproduction and disrupting the ROS/NF-κB signalling pathway, thereby attenuating inflammatory cytokine storms and ferroptosis. These results provide novel insights into the pathological mechanisms of bacterial sepsis in fish and develop sustainable strategies to improve disease resistance in aquaculture.
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LWT-FOOD SCIENCE AND TECHNOLOGY
·
2025
·
IF 6.6
Xin Chen,Zhengyang Zhu,Lishan Zhang,Xiaowei Zhang,Xin Zeng,Mengru Liu,Jinpeng Shi,Zhihan Yu,Siyan Chen,Shanshan Wang,Shujing Sun,Xiangmin Lin
The growing drug resistance of the fish pathogen Aeromonas hydrophila places a significant strain on aquaculture production and food safety. Paeonol, a plant-derived compound, exhibits substantial antibacterial potential. Our study shows that paeonol inhibits 12 bacterial strains, with an IC 50 of 256.8 μg/mL against A. hydrophila . Its antibacterial mechanisms include reducing bacterial motility, inhibiting biofilm formation, enhancing cell membrane permeability, and decreasing efflux pump activity. Proteomics revealed that efflux pump-related proteins were upregulated, while ABC transporter proteins were downregulated after paeonol treatment. Combining paeonol with efflux pump inhibitor (CCCP) enhances its antibacterial effects. Furthermore, the deletion of oppA , which encodes the periplasmic oligopeptide-binding protein in the ABC transport system, led to reduced survival of A. hydrophila under paeonol treatment, suggesting that paeonol interferes with the expression or function of OppA. A cell thermal shift assay (CETSA) further confirmed that paeonol binds to OppA, leading to the destabilization of the target protein. Notably, paeonol has low toxicity, minimal resistance induction, and high protective efficacy both in vitro and in vivo . It also reduces bacterial counts in fish meat, improving freshness. Overall, paeonol is a promising natural antimicrobial agent and food preservative for aquaculture production and food preservation.
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FISH & SHELLFISH IMMUNOLOGY
·
2023
·
IF 4.7
Lili Yun,Meiru Kang,Yihao Shen,Junchang Feng,Guokun Yang,Jianxin Zhang,Xiaolin Meng,Xulu Chang
This study aimed to evaluate the effects of dietary supplementation with Bacillus velezensis R-71003 combined with sodium gluconate on antioxidant capacity, immune response and resistance against Aeromonas hydrophila in common carp . In addition, the biocontrol potential of the secondary metabolites of B. velezensis R-71003 was also evaluated to analyze the possible mechanism of B. velezensis R-71003 against A. hydrophila . The results indicated that the antibacterial crude extract of B. velezensis R-71003 can destroy the cell wall of A. hydrophila . Moreover, the results showed that dietary B. velezensis R-71003 could promote antioxidant capacity, which significantly increased the activities of CAT and SOD and decreased the content of MDA. Additionally, B. velezensis R-71003 supplementation significantly enhanced the immunity of common carp, as measured by the mRNA expression levels of cytokine-related genes ( TNF-α , TGF-β , IL-1β and IL-10 ). In addition, dietary B. velezensis R-71003 exhibited an upregulation of IL-10 and a downregulation of IL-1β, coupled with higher survival rates when challenged with A. hydrophila compared to the positive group. Furthermore, compared to prechallenge, the mRNA expression levels of TLR-4 , MyD88 , IRAK1 , TRAF6 , TRIF and NF-κB in the head kidney of common carp were significantly increased after challenge. The fish fed the B. velezensis R-71003 diet showed lower expression of TLR-4 , MyD88 , IRAK1 , TRAF6 , TRIF and NF-κB after the challenge than those fed the control diet. Thus, this study revealed that B. velezensis R-71003 can improve the resistance of common carp to pathogenic bacteria by destroying bacterial cell walls and improving fish immunity by activating the TLR4 signaling pathway . Importantly, this study indicated that sodium gluconate has a positive effect on B. velezensis R-71003 in enhancing the anti-infection ability of common carp. The results of this study will lay the foundation for the application of B. velezensis R-71003 in combination with sodium gluconate as an alternative to antibiotics in aquaculture.
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npj Biofilms and Microbiomes
·
2020
·Vol. 6
·期 1
·1-12
·
IF 7.067
Dong Yuhao,Li Shougang,Zhao Dan,Liu Jin,Ma Shuiyan,Geng Jinzhu,Lu Chengping,Liu Yongjie
Aeromonas hydrophila is the causative agent of motile Aeromonad septicemia in fish. Previous studies have shown that the myo -inositol metabolism is essential for the virulence of this bacterium. IolR is a transcription inhibitor that negatively regulates myo -inositol metabolic activity. While in the process of studying the inositol catabolism in A. hydrophila Chinese epidemic strain NJ-35, we incidentally found that ΔiolR mutant exhibited obvious autoaggregation and increased biofilm formation compared to the wild type. The role of surface proteins in A. hydrophila autoaggregation was confirmed by different degradation treatments. Furthermore, calcium promotes the formation of aggregates, which disappear in the presence of the calcium chelator EGTA. Transcriptome analysis, followed by targeted gene deletion, demonstrated that biofilm formation and autoaggregation caused by the inactivation of iolR was due to the increased transcription of a RTX-family adhesion gene, rmpA . Further, IolR was determined to directly regulate the transcription of rmpA . These results indicated that iolR is negatively involved in autoaggregation and biofilm formation in A. hydrophila , and this involvement was associated with its inhibition on the expression of rmpA .
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